Sulfur is a constituent of many important polymeric materials, natural products, and synthetic reagents, providing impetus to devise efficient catalytic methodologies for sulfur-carbon bond formation. The addition of S—H bonds across alkynes is an atom-economical route to a variety of vinyl sulfides that can be achieved by several pathways, including radical (Capella, L. et al., J. Org. Chem. 1996, 61, 6783-6789; Benati, L. et al., J. Chem. Soc., Perkin Trans. 1995, 1035-1038; Benati, L. et al., J. Chem. Soc., Perkin Trans. 1991, 2103-2109; Ichinose, Y. et al., Chem. Lett. 1987, 16, 1647-1650; Griesbaum, K., Angew. Chem. Int. Ed. Engl. 1970, 9, 273-287) and catalytic processes (Sabarre, A.; Love, J., Org. Lett. 2008, 10, 3941-3944; Corma, A. et al., Appl. Catal., A 2010, 375, 49-54; Ananikov, Valentine P. et al., Chem. Eur. J. 2010, 16, 2063-2071; Shoai, S. et al., Organometallics 2007, 26, 5778-5781; Kondoh, A. et al., Org. Lett. 2007, 9, 1383-1385; Fraser, L. R. et al., Organometallics 2007, 26, 5602-5611; Delp, S. A. et al., Inorg. Chem. 2007, 46, 2365-2367; Beletskaya, I. P. et al., Pure Appl. Chem. 2007, 79, 1041-1056; Beletskaya, I. P. et al., Eur. J. Org. Chem. 2007, 3431-3444; Ananikov, V. P. et al., J. Am. Chem. Soc. 2007, 129, 7252-7253; Malyshev, D. A. et al., Organometallics 2006, 25, 4462-4470; Ananikov, V. P. et al., Russ. Chem. Bull. 2006, 55, 2109-2113; Ananikov, V. P. et al., Organometallics 2006, 25, 1970-1977; Cao, C. et al., J. Am. Chem. Soc. 2005, 127, 17614-17615; Ananikov, V. P. et al., Adv. Synth. Catal. 2005, 347, 1993-2001; Kondo, T. et al., Chem. Rev. 2000, 100, 3205-3220). Radical hydrothiolation yields unselective mixtures of E and Z vinyl sulfides, while organometallic catalysts offer access to Markovnikov vinyl sulfides or E anti-Markovnikov vinyl sulfides with varying degrees of turnover and selectivity (Misumi, Y. et al., J. Organomet. Chem. 2006, 691, 3157-3164). While diverse variants of organometallic complex-mediated hydroelementation have been extensively explored, including hydroamination, hydrophosphination and hydroalkoxylation, only recently has hydrothiolation been investigated in detail due to the historic reputation of sulfur as a catalyst poison (Hegedus, L. L.; McCabe, R. W., Chemical Industries Series, Vol. 17: Catalyst Poisoning. 1984), reflecting its high affinity for “soft” transition metal centers (Stephan, D. W. et al., Coord. Chem. Rev. 1996, 147, 147-208; Krebs, B. et al., Angew. Chem. Int. Ed. Engl. 1991, 30, 769-788).
Interest in homogeneous, catalytic alkyne hydrothiolation over the past few years has yielded a number of metal complexes competent to effect this transformation using late transition metal catalysts (Field, L. D. et al., Dalton Trans. 2009, 3599-3614; Ogawa, A. et al., J. Am. Chem. Soc. 1999, 121, 5108-5114; Kuniyasu, H. et al., J. Am. Chem. Soc. 1992, 114, 5902-5903). For example, Rh, Ir, Ni, Pd, Pt and Au complexes have been previously reported. While some late transition metal catalysts exhibit high activity, achieving high Markovnikov selectivity still presents a challenge, with the exception of Pd, as does competing isomerization of the alkene product, double-thiolation products and product insertion into a second alkyne. Furthermore, while some late transition metal complexes effect efficient alkyne hydrothiolation with benzyl and aryl thiols, few mediate hydrothiolation with the less reactive aliphatic thiols. Previous work with rhodium catalysts demonstrates the ability to utilize both terminal and internal alkynes with selectivity typically favoring the linear E anti-Markovnikov products with the exception of Tp*Rh(PPh3)2, where Markovnikov vinyl sulfides are selectively produced. Studies on group 10 metals find that nickel and palladium catalysts favor the Markovnikov product.
Available mechanistic data for late transition metal-mediated hydrothiolation complexes are consistent with pathways in which the alkyne undergoes insertion into either a metal-hydride or metal-thiolate bond. The accepted hydride pathway for most Rh complexes is initiated by π-coordination/activation of the acetylene to/by the metal-hydride complex, followed by alkyne insertion into the Rh—H bond. Finally, regeneration of the catalyst occurs through reductive elimination of product followed by RS—H oxidative addition to the metal center. Rhodium complexes selectively yield E anti-Markovnikov products as a result of the hydride insertion regiochemistry. In contrast, Pd complexes are proposed to effect hydrothiolation via acetylene insertion into the metal-thiolate bond followed by thiol-mediated displacement of product from the metal center, resulting in Markovnikov selectivity.
The efficacy of inexpensive organozirconium complexes for formally analogous hydroamination processes has been reported (Leitch, D. C. et al., J. Am. Chem. Soc. 2009, 131, 18246-18247; Smolensky, E. et al., Organometallics 2007, 26, 4510-4527; Ackermann, L. et al., J. Am. Chem. Soc. 2003, 125, 11956-11963; Arredondo, V. M. et al., Organometallics 1999, 18, 1949-1960; Majumder, S. et al., Organometallics 2008, 27, 1174-1177; Stubbert, B. D. et al., J. Am. Chem. Soc. 2007, 129, 6149-6167). Likewise, lanthanide complexes have also been used in hydroamination (Andrea, T. et al., Chem. Soc. Rev. 2008, 37, 550-567; Miller, T. E. et al., Chem. Rev. 2008, 108, 3795-3892; Hartwig, J. F., Nature 2008, 455, 314-322; Motta, A. et al., Organometallics 2006, 25, 5533-5539; Alonso, F. et al., Chem. Rev. 2004, 104, 3079-3160; Motta, A. et al., Organometallics 2004, 23, 4097-4104; Hong, S. et al., Acc. Chem. Res. 2004, 37, 673-686; Ackermann, L. et al., J. Am. Chem. Soc. 2003, 125, 11956-11963; Arredondo, V. M. et al., Organometallics 1999, 18, 1949-1960; Arredondo, V. M. et al., J. Am. Chem. Soc. 1999, 121, 3633-3639; Arredondo, V. M. et al., J. Am. Chem. Soc. 1998, 120, 4871-4872; Haskel, A. et al., Organometallics 1996, 15, 3773-3775; Giardello, M. A. et al., J. Am. Chem. Soc. 1994, 116, 10241-10254; Gagne, M. R. et al., J. Am. Chem. Soc. 1992, 114, 275-294), hydrophosphination (Perrier, A. et al., Chem. Eur. J. 2009, 16, 64-67; Douglass, M. R. et al., J. Am. Chem. Soc. 2000, 122, 1824-1825; Douglass, M. R. et al., J. Am. Chem. Soc. 2001, 123, 10221-10238; Kawaoka, A. M. et al., Organometallics 2003, 22, 4630-4632; Motta, A. et al., Organometallics 2005, 24, 4995-5003; Nagata, S. et al., Tetrahedron Lett. 2007, 48, 6637-6640; Sadow, A. D. et al., J. Am. Chem. Soc. 2004, 126, 14704-14705; Takaki, K. et al., J. Org. Chem. 2003, 68, 6554-6565; Wicht, D. K. et al., J. Am. Chem. Soc. 1997, 119, 5039-5040), and hydroalkoxylation processes (Motta, A. et al., Organometallics 2010, 29, 2004-2012; Dzudza, A. et al., Chem.-Eur. J. 2010, 16, 3403-3422; Seo, S. et al., Chem.-Eur. J. 2010, 16, 5148-5162; Cui, D.-M. et al., Synlett 2009, 7, 1103-1106; Dzudza, A. et al., Org. Lett. 2009, 11, 1523-1526; Janini, T. E. et al., Dalton Trans. 2009, 10601-10608; Nishina, N. et al., Tetrahedron 2009, 65, 1799-1808; Seo, S. et al., J. Am. Chem. Soc. 2009, 131, 263-276; Zhang, Z. et al., Org. Lett. 2008, 10, 2079-2081; Nishina, N. et al., Tetrahedron Lett. 2008, 49, 4908-4911; Harkat, H. et al., Tetrahedron Lett. 2007, 48, 1439-1442; Yu, X. et al., J. Am. Chem. Soc. 2007, 129, 7244-7245; Zhang, Z. et al., J. Am. Chem. Soc. 2006, 128, 9066-9073; Yang, C. G. et al., Org. Lett. 2005, 7, 4553-4556; Qian, H. et al., J. Am. Chem. Soc. 2004, 126, 9536-9537). However, the use of these complexes in the hydrothiolation of alkynes has yet to be reported.
Accordingly, an efficient catalytic system is desired for the hydrothiolation of terminal alkynes by aromatic, benzylic, and less reactive aliphatic thiols. This system should proceed with a high degree of Markovnikov selectivity and reduce 1) the formation of double-thiolated side product, 2) the competing isomerization of the alkene product, and 3) the product insertion into a second alkyne.